U.S. Pat. No. 5,095,149 describes a process for the preparation of 4-halogeno-2-methoxyimino-3-oxo-butyric acid of formula (I) by brominating the methoxy imino compound of general formula (III) by bromine in mixture of IPE and ethylene dichloride. Ethylene dichloride is a toxic solvent and hence its use in the preparation of pharmaceuticals has to be avoided.
U.S. Pat. No. 5,109,131 describes a process for the preparation of 4-halogeno-2-methoxyimino-3-oxo-butyric acid of formula (I) starting with the reaction of diketene and, tert-butyl alcohol, followed by oximation, methylation, hydrolysis and halogenation. This method involves the hydrolysis and halogenation in two steps.
Synthesis of 4-halogeno-2-methoxyimino-3-oxo-butyric acid is reported in patent no. EP 0 030 294 and a large number of references are available in the patent literature disclosing the use of 4-halogeno-2-substituted imino-3-oxo-butyric acid represented by formula (I) as the starting material. EP 0030294 discloses the condensation of the 4-halogeno-2-substituted imino-3-oxo-butyric acid represented by formula (I) with cephem carboxylic acids by using PCl5. Another EP patent 0 842 937 discloses the formation of amide bond with cephem moiety by reacting with the thioester derivative of 4-chloro-2-methoxyimino-3-oxo-butyric acid. The thioester was prepared by reacting 4-chloro-2-methoxyimino-3-oxo-butyric acid with 2,2′-dithio-bis-benzothiazole in the presence of triphenyl phosphine which is a costly material and its by product triphenyl phosphine oxide is also difficult to remove from the reaction mixture.